Devices for occluding channels in living mammals

ABSTRACT

A method of blocking channels in a mammal which channels normally carry a material from one point to another is carried out by injecting a heated flowable polymer into the channel and allowing the polymer to cool and solidify, thus creating a plug or channel occluder. The plug can be later removed physically in its solid form or removed gradually by softening and/or fluidizing it by heating and/or chemical means. The channel occluder is preferably comprised of a main chain or side-chain crystallizable polymer but may be comprised of other polymers provided the polymers are formulated to have certain characteristics. The polymers must be solid and/or non-flowable at body temperature or lower and flowable when heated slightly above body temperature, i.e., 10 centigrade degrees or less above body temperature. The polymer is capable of changing quickly from a flowable state to a non-flowable state by moving through only a few centigrade degrees of temperature and is a non-immunogenic, biocompatible material. Typical channels which may be reversibly occluded via the present invention include the vas deferens, the mature sperm excretory channel of the testis; the fallopian tube or oviduct, the viaduct conveying the ovum from the ovary to the uterus; the canaliculus lacrimalis, the passageway that allows excess tears to flow from the puncta of the eye to the lacrimal sac; and the cavity of the femoral shaft to fix the stem of replacement hip joint (ball and neck).

This is a division of application Ser. No. 07/939,110, filed Sep. 2,1992 now U.S. Pat. No. 5,469,867.

FIELD OF THE INVENTION

This invention relates generally to the field of medical devices andmethods of treatment using such devices, and more particularly relatesto thermoplastic polymeric or composite channel occluders and methods ofoccluding channels in living mammals by forming such channel occludersin situ.

BACKGROUND OF THE INVENTION

All mammals include a variety of channels for moving fluids or materialsfrom one location within the body to another. In general these channelsare called tubes, ducts, foramina, cavities, canals and vessels some ofwhich have internal flow controls i.e., sphincters, capillary bed, etc.Specifically these channels include fallopian tubes, naso-lacrimalducts, blood vessels, vas deferens, cavities within the bone and thelike. Unless these channels are diseased, surgically altered or damagedin some manner, they continue to provide a means for conducting fluid ormaterial through them for at least part of the time. If they aresurgically altered, it may become important to secure a prostheticelement in place. Such channels may be voluntarily closed by the mammalsuch as by muscular movements or contractions. However, they all remainopen part of the time. There are certain advantages to overriding thenatural physiology for a sustained period of time and completely closingoff particular channels in order to obtain particular desirable results.Depending on the particular channel to be closed, a number of differentprocedures have been developed in order to temporarily or permanentlyclose such channels, with or without securing prosthesis in place. Someof these procedures are described below.

Blocking the Canaliculus

Mammalian eyes include a complex composition in the form of a tear film.Tears include three basic component layers comprising (1)lipids, (2)anaqueous layer, and (3)mucin. The absence of any one of the layercomponents causes discomfort and can lead to temporary or permanent dryeye syndromes (SICCA). Each of the component layers has a particularfunction. The lipid layer prevents evaporation of the tears from thesurface of the eye. The aqueous layer is the major component of thetears, and is responsible for providing oxygen to the cornea andcontains a number of additional chemical components which are importantto a healthy eye. The mucin material provides for interaction betweenthe lipid layer and the aqueous layer and keeps the tears from beadingup on the cornea, which will occur in the absence of mucin.

The importance of a tear layer on a healthy mammalian eye can begenerally understood based on the above explanation. However, from timeto time the eye suffers from a lack of tears (dry eye), which can have avariety of causes but is generally attributed to one or two basicmalfunctions. First, the tear ducts leading from the lacrimal glands canbe clogged or malfunctioning so that insufficient amounts of tears reachthe eye. This was generally thought to be the main reason for dry eyefor a considerable period of time. In response, artificial tears weredeveloped and administered to eyes. The relief enjoyed by these tearsare short-lived and must be readministered several times each hour. Morerecently, it has been noted that most tear producing glands can deliversufficient amounts of tears to the eye, but that the tears are drainedaway from the eye too quickly, thereby creating a dry eye situation.Accordingly, recent therapies have proceeded on the basis that tearproduction is adequate in most individuals, and that a significantpercentage of dry eye syndrome is caused by excessive tear removal.

Tears are removed from the eye by draining first through upper and lowerpunctal openings which lead into the canalicular canals. Initialattempts at sealing the puncta and/or the canalicular canals involvedstitching the puncta shut or using electrical or laser cauterization toseal the puncta and or canalicular canals. Although such methodology canprovide desirable results, the procedure is not reversible withoutreconstructive surgery. Since it is sometimes difficult to determinewhether the drainage is too great or the tear production is too small,irreversible blockage is a condition which is not without risk. If tearproduction is completely eliminated, it will not solve the problem andthe patient would have been exposed to unnecessary expense and trauma.Alternatively, it can result in a situation where normal tear flow isrestored and tears continually form on the eye, build up and pour ontothe face of the patient. (epiphera)

In order to provide for an autoreversible technique for sealing thepuncta or canalicular canals, collagen implants were developed. Theseimplants were designed to be water soluble and were placed in the punctaand/or canalicular canals in order to provide for a test procedure onthe patient. Over a period of seven to fourteen days, the implantsdissolved. The patient was observed over this time, and it wasdetermined whether it would be desirable to permanently seal the puncta.

Water-insoluble plugs which can be placed in the punctum openings andinto vertical sections of the canalicular canals are disclosed withinU.S. Pat. No. 3,949,750 to Freeman. Although these plugs are reversible,they tended to become dislodged quite easily. Further, they are somewhatdifficult to insert, and occasionally their size and shape can causetissue damage during insertion or, if they protrude from the puncta,they can cause irritation to the sclera. The tissue of the punctum canalso be damaged by being dilated by the plugs over long periods of time.

An improvement on the Freeman plugs is disclosed within U.S. Pat. No.4,959,048 to Seder et al., issued Sep. 25, 1990. Seder et al. disclose apreformed plug or channel occluder which is somewhat conical in shape,making it possible to insert the occluder into the opening of thepunctum more easily than the devices disclosed by Freeman. Further,Seder et al. disclose that variations in the anatomy of individuals makeit desirable to provide a series of occluders which are provided indifferent lengths and/or widths in order to accommodate the anatomicaldifferences. Further, the surface of the plugs may be coated with alubricant.

Occluding Reproductive Channels

The mature sperm of mammals moves through excretory channels of thetestes which are referred to as the vas deferens. A well-known means ofmale contraception is achieved by carrying out a procedure referred toas a vasectomy, wherein the vas deferens are severed or sealedsurgically. Once the channel has been severed, it is difficult toreconnect channels so that they can function properly. In order toattempt to provide some degree of reversibility with respect to thisprocedure, mechanical valves have been developed and inserted into thevas deferens in a manner which interrupts the flow of sperm through theduct channel. Although this procedure provides a degree of reversibilityin that the valves can be opened or closed, the procedure is not withoutdifficulties. First, it is extremely difficult to produce such smallvalves and to insert them within small channels in a manner which doesnot damage the channels while making sure that the valves can later bereopened and allow the channels to operate normally. Further, the sealcreated by such valves is sometimes not complete. Maintaining a healthy,viable seal between living tissue and an inert organic prosthetic deviceis difficult to accomplish when the device is not designed to conformprecisely to the size and shape of the duct channel.

Methods of rendering female mammals infertile include tying ligaturesaround the fallopian tubes. Thermosetting silicones have been used tofill these tubes to render women infertile. Alternatively, the surfacesof the tubes may be chemically or thermally scarred in such a mannerthat after healing, the duct channel is closed, preventing the movementof eggs through the channel. In order to reverse such procedures, it isnecessary to attempt to remove the damaged portion of the duct channeland surgically connect undamaged ends in a manner so as to provide for ahealthy, functionally operating channel. Although a high degree ofsuccess is obtained with respect to sealing fallopian tubes, the degreeof success with respect to reversing the operation is relatively low.

Closing Off a Blood Supply

In the case where a patient has developed a tumor in an organ, that isinaccessible or the organ is of a nature or in a position that preventsa surgical approach, a method to rid the host of the problem may be tocut off the blood supply and starve the unwanted growth. Rapidlypolymerizing monomers such as methyl α-cyanoacrylate can be deposited inthe appropriate vessel by means of an appropriately guided cannula orcatheter. When the end of the catheter is in the proper position, themonomer is released. Once exposed to the multitudinous supply ofnucleophilic natural agents, the monomer polymerizes and effectsblockage. However, the monomer itself is toxic and causes acuteinflammation and necrosis to the surrounding tissues. The trauma itselfenlists a reaction which causes vascularization to the area and soon thetumor is once again well nourished. In the case where a patient hasdeveloped an uncontrolled hemorrhage in, perhaps, the brain, there istoo much risk to attempt surgical intervention. The safest way to arriveat the site of hemorrhage is again by a fine guided catheter. A rapidlypolymerizing monomer such as methyl α-cyanoacrylate can be deposited inthe appropriate vessel at the site of hemorrhage. While the polymerizingmonomer is effective in shutting down the blood flow through the brokenvessel, it sometimes causes the tip of the catheter to become cementedin place.

Correction of Vascular Abnormalities

A condition known as arteriovenous anastomosis (the joining of an arteryand a vein) is a serious problem because anastomosis bypasses theintended capillary bed thus starving the cells fed by that system. Oncerecognized, the surgeon will attempt appropriate measures to correct thecondition. Closing off that abnormality by surgery is direct if the areacan be accessed. Usually guided catheterization is used when theidentified anastomosis is remote or in accessible. Gelling agents areused but they are normally difficult to repair because of the high flowrate through the abnormality. A quick set time creating a permanent plugis very attractive. A cyanoacrylate can be deposited in the appropriatevessel at the site but the method suffers from the risks as describedabove.

Closing up a Temporary Channel Made for a Cranial Tap

Not all channels need to be provided to the mammalian body by nature.Some could be man-made channels for example, a temporary cranial tap topermit the release of pooled blood between the brain and the skull aftera concussion. After the pressure is reduced, the hole must be sealed toprevent the passage of other fluids or bacteria getting into the brain.A plastic shield may be placed over the channel before the skin ispulled over it and sown closed.

Fastening a pin in the lumen of a bone

Broken bones are frequently supported by steel pins placed within thenatural lumen of a finger or limb bone. Hip joint replacements usuallyrequire that a new ball fitting be placed at the end of the femur bymeans of a pin or spike. This spike enters the lumen of the femur. Ineither case, if the fit is not tight, cement or mastic is used to fillin the space between the pin and the bone to keep the pin in positionand prohibit it from moving within the lumen.

The above is not, and is not intended to be, an extensive discussion ofall of the different types of channels present within living mammals.Further, the above is not, and is not intended to be, a discussion ofall the different types of techniques and procedures and devices whichcan be used to seal such channels in order to obtain results which maybe permanently or temporarily desirable. The above merely provides somelimited background information on six particular types of channels foundin living mammals, which channels are occluded or sealed by medicalprocedures and/or devices. Further, the above indicates that by carryingout these procedures and/or using these devices, results which are seenas desirable can be obtained. The present inventor endeavors to providenew techniques and devices for sealing channels within mammals whichprovide a number of advantages.

While the subject of body temperature is a complex one, (see BodyTemperature Regulation, Medical Physiology, eleventh edition Philip BardEd., C. V. Mosby 1961.), several features should be called out. First,the average core temperature of humans is not a very consistent number.It varies for individuals over a range of 36° C. to 38° C. However,normal healthy men or women after vigorous exercise can raise theirtemperature to as high as 42° C. In the morning when the externalsurroundings are cool, the body temperature can drop to below 33° C.Extremities such as feet can achieve temperatures of 27° C. when thesurroundings are cool.

Second, the temperature at which denaturation of cells occurs varieswith the section of the body involved and the time over which the cellsare exposed to that heat. The brain is perhaps the most sensitive organ.Brain lesions and heat stroke occur in the range of 42° C. to 44° C.Bones can withstand the exotherm created by polymerizingmethylmethacrylate which may exceed 60° C. Most cells can withstand 45°C. temperatures for several minutes without any harmful effects as wellas they can tolerate 50° C. for several seconds.

With this background the inventor now can reveal the basis of thisdisclosure.

SUMMARY OF THE INVENTION

A method of occluding channels in a living mammal by forming channeloccluders in situ is disclosed. A variety of channels in living mammalssuch as the canalicular canals, vas deferens, fallopian tubes, femoralcavity and arteries are all capable of moving fluids or materials fromone point to another within a living body. In accordance with theinvention, a special polymeric material or composite of such, whichexhibits the special characteristic of being a flowable viscous liquidbetween the average temperature of the site and 50° C. and arheologically stable solid at or below the average temperature of thesite is used. These new techniques and devices must operate and functionbetween the temperature of the host channel and the temperature at whichcells and structures begin to disintegrate or denature. In practice, thespecial polymer or composite is heated to a point where the material isflowable (the preplug) and is then loaded into an injecting device. Theinjecting device can be maintained warm or above the transitiontemperature so that the polymeric material or composite of such nevercools below transition temperature and solidifies. Also the device andits contents can be alternately cooled and heated so that the polymericmaterial or composite of such solidifies and then remelts. The processcan be repeated as often as is willed. While in a flowable state, thematerial (preplug) is injected into the living channel which is to beoccluded. The polymeric material or a composite of the same cools inplace within the channel and solidifies, forming a plug which blocks thechannel. The plug can be removed, making the blocking procedurereversible, by physically withdrawing the plug from the channel, heatingthe plug such as by the application of an electrical heating devicewhich melts the polymer, or applying a lipophilic compound such as anoil or a fatty acid ester which dissolves into the polymer and reducesthe melting point of the polymer to a point at or below bodytemperature, thereby transforming the plug into a flowable fluid that isremovable by the normal flow movement characteristics of the channel orby irrigation with saline solution and the like. The channel occludercan be inserted within the canalicular canal in order to prevent dryeye, the vas deferens or fallopian tubes to provide a means ofcontraception, or inserted within arteries in order to block the bloodflow to a tumor area or to plug up a hemorrhage in the brain, liver orspleen or to correct an abnormality such as arteriovenous anastomosis orto close over a tap hole in the skull or to fix a stem, pin or spikewithin the lumen of a bone. The procedures are primarily designed forhuman application but can be carried out on other mammals such ascanines, race horses and felines which a breeder may wish to renderinfertile only on a temporary basis or to which a veterinarian mayattempt to extend the quality of life or life itself.

An important object of the invention is to provide a method of occludinga channel in a living mammal.

Another important object of the present invention is to provide achannel occluder which is formed in situ in order to block or close achannel in a living mammal such as a human.

An important advantage of the present invention is that the channeloccluder can be formed in situ in the lumen of the channel with aminimum degree of trauma to the patient.

Another important advantage of the present invention is that because thechannel occluder is formed in situ against the channel wall, a perfectfit is achieved between the plug and the wall thus assuring that nopassage of any biological fluids or substance will be allowed.

Another important advantage of the present invention is that because thechannel occluder is formed in situ against the channel wall, a perfectfit is achieved between the plug and the normally convoluted wall thusassuring that no movement of the plug will occur with time.

Another important advantage of the invention is that no catalyst,monomers, curing agents or other toxic agents need be present to effectthe change between the liquid and solid state of the plug, thuspreventing any possible chemical injury to the surrounding tissue.

Another important advantage of the invention is that no exotherm isneeded to effect the change between the liquid and solid state of theplug, thus preventing any possible thermal injury to the surroundingtissue.

Another important advantage of the invention is that any variation inthe size of the channel from one subject to another can be accommodatedbecause the flowing preplug completely fills the lumen of the channelbefore it solidifies. There is no need to match a specific internaldiameter with different sized plugs. There will always be a perfect fit.

Another important advantage of the present invention is that the channeloccluder can be removed from the lumen of the channel without subjectingthe channel or the patient to significant trauma and/or discomfort.

An important feature of the present invention is that the channeloccluder is comprised of a polymeric or composite material which isflowable at only a few degrees centigrade above body temperature and issolid at body temperature and below, thus preventing any possible injuryto the surrounding tissue.

Another important feature of the present invention is that the polymericor composite material can be selected from a variety and range ofcrystallization rates from several seconds to several minutes.

Another important feature of the present invention is that the polymericor composite material can be selected from a group that exhibits avariety and range of temperature transitions from about 30° C. to about50° C.

Another important feature of the present invention is that the polymericor composite material is non-immunogenic and biocompatible.

Another advantage of the present invention is that the channel occludertakes on a shape which conforms with the size and shape of the channelbeing blocked, providing a secure, uniform fit within the duct channelwithout substantial dilation of the duct channel.

Another important advantage of the invention is that the channel can beblocked with a non-immunogenic, biocompatible polymer or compositewithout damaging delicate tissue on the internal surface of the ductchannel or tissue surrounding the duct channel.

These and other objects, advantages and features of the presentinvention will become apparent to those persons skilled in the art uponreading the details of the methods, devices and processes as more fullyset forth below, reference being made to the accompanying figuresforming a part hereof.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic view showing the lacrimal duct channel teardrainage system of a mammalian eye;

FIG. 2 is a schematic view of an injecting device of the presentinvention inserting polymeric material into the canalicular canal;

FIG. 3 is a cross sectional schematic view of the canalicular canalsblocked with duct channel occluders of the present invention;

FIG. 4 is a schematic cross sectional view of channel occluder materialpassing through a fine catheter showing the catheter is fitted with aheater element at the end;

FIG. 5 is a schematic cross sectional view of the human femoral bonethat had the defective superior joint process removed and an enlargedchannel made within the healthy portion of the bone;

FIG. 6 is a schematic cross sectional view of the human femoral bonethat has been partially fitted with the channel occluder of the presentinvention and, proximal to it, a prosthetic device designed to replacethe defective joint process; and

FIG. 7 is a schematic cross sectional view of the human femoral bonethat has been fitted with the prosthetic device showing the spaceremaining between the device and the bone has been occluded by thematerial of the present invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

Before the present channel occluder and methodologies and processes formaking and using same are described, it is to be understood that thisinvention is not limited to the particular methods, polymers,composites, channels and processes described as such may, of course,vary. It is also to be understood that the terminology used herein isfor the purpose of describing particular embodiments only, and is notintended to be limiting since the scope of the present invention will belimited only by the appended claims.

Throughout the disclosure, unless the context clearly dictatesotherwise, the terms "a" "an" and "the" include plural referents. Thus,for example, reference to "a polymer" includes mixtures of polymers andstatistical mixtures of polymers which include different weight averagemolecular weight polymers over a range, reference to "an occluder"includes one or more occluders or plugs, and reference to "the channel"includes one or more channels, the same or different types, and soforth.

Unless defined otherwise, all technical terms and scientific terms usedherein have the same meaning as commonly understood by one ordinarilyskilled in the art to which this invention belongs. Although any methodsand materials similar or equivalent to those described herein may beused in the practice or testing of the present invention, preferredmethods and materials are described below. All publications mentionedherein are incorporated by reference. Further, specific terminology ofparticular importance to the description of the invention is definedbelow.

Definitions

The terms lumen, canal, foramen, tube and duct are used interchangeablyherein to describe various channels, passages, openings, cavities orspaces within a living mammalian species through which fluid or materialmay move from one location to another. The opening is generallycylindrical in dimension with specific non-limiting examples of suchchannels found within the canalicular canals, vas deferens, fallopiantubes, arteries of the liver, kidney and brain. In most cases, thechannels are provided to the mammalian body by nature. However therecould be some man-made channels for example, a temporary cranial tap.The material that may pass through the channel does not have to beindigenous to the host either. For example it could be a steel pinwithin a cavity of a bone. The plug would form between the pin and thebone to keep the pin in position so that it would not pass from thelumen.

The term "occluding a channel" refers to the process of partially and/orcompletely filling at least a portion or section of a channel, passage,opening, cavity or space with a substance that hinders and/or completelyprevents the transport or movement of another substance through thechannel. This "other substance" could be biological in origin such assperm, ova, tears or blood or it could be a prosthetic device such as ametal rod or pin. In preferred embodiments the channel is completelyblocked and prevents all flow through.

The term "biologically inert" suggests that no acute physiologicalactivity is observed in response to the presence of the material orsubstance described as possessing such a property. Examples ofunacceptable physiological activity would include surface irritation,cellular edema, etc.

The terms "polymer" and "polymeric material" are used interchangeablyherein to refer to materials formed by linking atoms or moleculestogether in a chain to form a longer molecule, i.e., the polymer. Thepolymers are preferably biologically inert, biocompatible andnon-immunogenic. A range of different polymeric materials can be used inconnection with the invention provided they have certain characteristicswhich include having a melting point which is about or above bodytemperature but only above body temperature by an amount of 10centigrade degrees or less. The particularly preferred polymericmaterials are biocompatible, non-immunogenic and not subject tosubstantial degradation under physiological conditions.

The terms "polymer", "polymer composition", and "composite" areinterrelated. The "polymer composition" refers to either the polymer ofpolymeric material itself as defined above or a composite as definedbelow.

The term "composite" refers to a combination of a polymer with (1) abiologically inert substance that need not qualify as a "polymer" butmay have the special characteristics of having a melting point abovebody temperature and may have the ability to toughen or act as a heatsink for the polymer or be radio-opaque. These biologically inertsubstances or "fillers" are, for example, spherical particles of gold,silver powder, a radio-opaque pigment or fumed silica. The term"composite" also refers to a combination of a polymer with (2) abiologically active substance that could leach out of the solid occluderonce formed in the channel. These biologically active substances couldbe blood coagulating compounds, spermicides, growth promoting hormones,antibiotics and the like.

The term "melting point" refers to the temperature at which the peak ofthe endotherm rise is observed when the temperature is raised throughthis first order transition.

The term "plug" refers to the polymer, polymeric material or compositein its solid form below the crystalline melting point and in the shapeand dimensions of the channel which it fills.

The term "preplug" refers to the polymer, polymeric material orcomposite in its fluid form or state above the crystalline melting pointand takes the shape and dimensions of the container or injecting devicewhich holds it.

The term "chamber" refers to central holding portion of the device usedto deploy the occluder material.

The term "orifice" refers to the exit port leading from the chamber tothe delivery end of the device.

The term "injecting device" includes any device capable of holding orcontaining the preplug of polymer materials or composites of the presentinvention in its chamber, while, before or after such a polymer materialis heated to a flowable state and is further capable of being used toinject or extrude the polymer materials from that container in which itis held into the duct or channel to be blocked. Specific examples ofsuch devices include all types of hypodermic needles, pointed plastictip applicators, reservoirs, plungers, release systems and syringes.

Main chain crystallizable polymers (MCC polymers), are useful for thisinvention are well-known and, some of which, are available commercially.They are reviewed by Robert W. Lenz, "Organic Chemistry of SyntheticHigh Polymers", John Wiley & Sons, New York, 1967, pp 44-49.

Side chain crystallizable polymers (SCC polymers) are particularlyuseful for this invention and are sometimes called "comb-like" polymers,are well-known and, some of which, are available commercially. Thesepolymers are reviewed in J. Polymer Sci.: Macromol. Rev. 8:117-253(1974), the disclosure of which is hereby incorporated by reference. Ingeneral, these polymers are characterized as having a crystallizablecluster off to the side of the main backbone and can be made in severalconfigurations, i.e. homopolymers, random copolymers, block copolymersand graft copolymers.

Thermoplastic "block" polymers may have enhanced toughness or displaygood elastic properties below the melting point and are frequentlyreferred to as thermoplastic elastomers or TPE's.

The polymeric hard block used in the synthesis of some of the graftcopolymers are referred to as Macromers.

The first order transition is the melting point of the crystallinedomains of the polymer. The peak developed in the trace of adifferential scanning calorimeter analysis experiment has been used todefine this transition.

The flow point of a material is the temperature at which the viscosityis low enough to be observed to flow after the solid is brought throughits melting range at a temperature rise of 10° C./minute. For theclasses of polymers described in this invention the flow point isgenerally 2° C. to 6° C. above the first order transition.

General Description of Methodology

In general, the method of the present invention could be used to blockany type of channel, i.e., block channels within living and non-livingbeings of any type and block all types of channels and tubular deviceseven outside of biological systems. The essence of the invention relatesto blocking channels within things, living mammals or human beings inorder to prevent movement of a substance into or out of a channel withinthat host using a material that both flows and solidifies within thevery narrow temperature band defined by (1) the normal temperature ofthe host and (2) the temperature at which thermal damage is done to thewalls of the channel thereby obtaining beneficial effects. The inventionnaturally focuses on and has the greatest need in treating mammalianconditions because of the extreme narrowness of breath between normalbody temperature (30°-40° C.) and the temperature range in which thermaldenaturation and damage begins. (45° C.-50° C.)

The first step in the method of the invention is to provide a polymerwhich is preferably a biocompatible, non-immunogenic polymer and toplace such polymer within an injecting device of some sort. The polymershould be selected so as to have a melting point (1) sufficiently highthat the polymer is a non-flowable solid at the normal temperature ofthat channel and (2) sufficiently low that melted polymer can beinjected into the channel in a flowable form without thermally damagingthe cells of the mammal. The polymer can be blended with other materialsto produce a composite. The polymer can be formed into a thin rod orcylinder and inserted in a channel as it is undergoing a transition to afluid form but is preferably injected into the channel. A range ofdifferent types of injecting devices can be used such as plastic tubes,catheters, fine cannula, tapered cannula and various types of syringesand hypodermic needles which are generally known to and available tothose in the medical profession. The amount of the polymeric materialprovided in the injecting device will vary somewhat depending on theparticular channel to be blocked and the amount and type of blockagedesired. Those skilled in the art will be aware of the size of thechannel being blocked based on the size of the patient and generalknowledge of anatomy and will be able to judge the amount of polymermaterial to be included within the injecting device. In general, anexcess amount of material should be included in the injecting device inorder to provide for a certain margin of error.

The polymeric material may be included within the injecting device in asolid form or heated and provided in the injecting device in a flowableform. In one preferred embodiment, the injecting devices can beprepackaged with the polymeric material present therein and thereafterheated in order to make the polymeric material flowable. Heating can beapplied (1) from an exterior source such as an air, water or oil bath oran electrical heater. In this case, the injector as well as the occludermaterial are both heated. Heating can also be applied (2) from aninterior source such as a small electrical resistive element at the endof a catheter through which a thin rod of the solid occluder material isbeing passed or such as a small laser beam directed at the tip of asolid rod of occluder material emerging from the end of a catheter. Theinjecting device includes an extrusion nozzle which is preferablyrelatively small in diameter such that it will not seriously damage thechannel to be blocked but sufficiently large such that the polymericmaterial can be freely extruded from the nozzle.

The size of the nozzle is generally related to the inside diameter ofthe channel into which it is placed. For example, a 24 gauge needleeasily fits within the opening of the punctum which leads to thecanaliculus. A 2 mm catheter is appropriate for introducing the prepluginto the fallopian tubes. A 1/4 inch cannula is recommended forintroducing the preplug into the inner cavity of an adult humorous. Theviscosity limitation of the preplug is dependent upon the size of theorifice that the preplug must pass through. In general, the smaller theorifice the lower the viscosity must be.

Once the polymer has been included within the injecting device andheated to a flowable state, the nozzle of the injecting device such asthe tip of a needle or devise is inserted into the channel opening orthrough the wall of the channel to be blocked and the polymer isinjected out of the nozzle into the chamber of the channel. Theinjection is continued until the desired amount of blockage is obtained.In some instances, it may be desirable to only block part of thechannel, i.e., allow partial flow. However, in general, the entirechannel is to be blocked. Accordingly, the polymer will generally beinjected into the channel so as to completely fill the channel and allowthe polymeric material to conform to the internal surface walls of thechannel being blocked. Thereafter, the nozzle of the injecting device iswithdrawn.

After the polymer has been injected, the remainder of the process willoccur without interaction. More specifically, the circulatory system ofthe mammal will cause a cooling effect on the surrounding tissues whichwill cool the injected polymer. The polymer is designed such that itcools and solidifies after losing only a small amount of energy, i.e.,hardens after decreasing in temperature by only a few centigradedegrees. Usually, the process takes only a few seconds or minutes tooccur although there are times when it may be better to take longer,i.e. in the case where the preplug must flow through a long catheter orwhere a bone must be reset etc. After cooling has taken place, thepolymer solidifies within the channel in a manner conforming to theshape of the channel and the channel is blocked. The duct channeloccluder formed in the channel can remain in place in the channel overlong periods of time. In that the polymer is comprised of abiocompatible, non-immunogenic material, no adverse reaction isobtained. Further, the polymer is designed such that it is notsubstantially deteriorated under physiological conditions.

One of the important advantages of the method of the present inventionis that the duct channel occluder can be readily removed so as to againprovide a channel which functions in a normal manner. The duct channelcan be removed by a number of different means. Firstly, the duct channelmay be removed by simple mechanical extraction. In certain instances,devices such as forceps and/or catheters with various attachment prongsconnected thereto can be inserted into the channel and used to attach tothe plug and pull the plug out of the channel or force it forward intoanother chamber where the channel will not be blocked and the plug willnot cause any damage. Alternatively, a device such as a wire which actsas a heating coil can be brought into contact with the solidifiedpolymer plug. By heating the material with the heating coil, thetemperature of the material is raised above body temperature and abovethe first order transition point of the polymer so that the polymeragain becomes flowable. The heating is continued until the flowablepolymer flows from the channel and the channel is reopened to providenormal function. In certain circumstances, the liquid plug can be coaxedout of the channel. It can be made to stick on a fine wire as itscooling, hence the occluder is removed as the wire is withdrawn or itcan be suctioned out with a gentle vacuum or it can be forced out usingmild pressure created by air or a saline flow.

A particularly preferred method of removing the solidified polymer plugis to inject a lipophilic material such as a naturally occurring oil ora fatty acid ester into the channel in the area surrounding thesolidified polymer. The lipophilic material will migrate into anddiffuse within the polymeric material. When the lipophilic material andthe polymer have interspersed, the lipophilic material will cause thefirst order transition point of the polymer to be lowered, i.e., causesthe plug to have a decreased melting point. Sufficient amounts of thelipophilic material can be added such that the first order transitionpoint of the polymer will drop well below body temperature and thepolymer will become flowable. Once the polymer becomes flowable, thenatural mechanical movement which occurs within channels of livingbeings will move the polymer from the channel and the polymer will beremoved and the channel will be restored to its normal function.

Treating Dry Eye

As described in the "Background of the Invention" section of thisapplication, the ability to maintain healthy eyes is largely dependenton the ability to maintain a sufficient amount of tears on the surfaceof the eye. When the amount of tears present is decreased below normallevels, a number of adverse effects can result. Thus, it is desirable totreat the cause of "dry eye". If the "dry eye" is occurring due to theinability of the tear ducts channels to produce any tears, then thepresent invention cannot be used in order to treat the patient. However,in most cases, the tear ducts channels will produce some tears and inmany cases the tear ducts channels will produce sufficient amounts oftears provided the tears are not drained away from the surface of theeye too quickly. When the tear duct channel is producing some tearsand/or normal amounts of tears that are being drained away too quickly,the present invention can be used.

By referring to FIG. 1, the lacrimal tear duct channel drainage systemof a mammalian eye can be seen. As shown within FIG. 1, the drainagesystem includes a lower punctum 1 connected to a canalicular channel 2and an upper punctum 3 connected to a canalicular channel 4. Tears whichsurround the eye 5 are continually drained from the area surrounding theeye into the punctum 1 and 3 and through the canalicular channels 2 and4. The tears are eventually drained downward into nasal cavities.

When the tear duct channel produces insufficient tears or the punctum orchannels become too large and drain the tears too quickly, dry eyeresults. The present invention can be used in the manner as shown withinFIG. 2. As described above, the polymer material is included within aninjecting device and heated to a flowable state. The end of the nozzle 6is shown inserted through the lower punctum 1 and into the canalicularchannel 2 where the polymer 7 is injected. Injection of the polymer 7 iscontinued until the channel 2 is filled. In order to provide for a snugfit, it is possible to inject enough polymer to fill the channel andwait for the polymer to solidify. Thereafter, additional polymer isadded in order to overfill the channel while allowing the originalpolymer deposit to act as a blocking dam. When the channel isoverfilled, the polymer forms a plug which conforms to the size of thecanalicular channel. As shown within FIG. 3, both canalicular channels 2and 4 can be filled and completely blocked.

Once the polymer plugs 7 have been placed in the channels 2 and 4, thetears will not drain so quickly form the area around the eye. Thus, thedry eye abnormality should be eliminated. If this treatment is notsuccessful in eliminating the abnormality, it may be desirable to removethe polymeric plugs 7. This can be done in a variety of different meanssuch as those indicated above. One means of eliminating the plugs is tosimply use a mechanical means to attempt to extract the plugs outward orto force the plugs downward into the nasal passageways. Alternatively,the plugs can be made flowable by heating or the injection of a material(such as fatty acid esters) which dissolves or decreases the meltingpoint of the plugs below body temperature.

Methods of Contraception

It is well known that male contraception can be carried out byinterrupting the flow of sperm through the vas deferens. Further, femalecontraception can be obtained by interrupting the flow of eggs from theovarian through the fallopian tubes. Accordingly, the present inventioncan be utilized in order to temporarily sterilize either male or femalemammals by blocking either the vas deferens or fallopian tubes.

The methods of carrying out the contraceptive means of the presentinvention are substantially the same as the general method describedabove and the specific method described with respect to blocking thecanalicular canals. Those skilled in the art will recognize that thereare differences in sizes between the different channels and useappropriate amounts of polymers necessary to block the channels.Further, those skilled in the art will recognize that effectivecontraception cannot be obtained unless the channels are completelyblocked. Accordingly, more diligent efforts should be made in order tocompletely fill the channels with respect to their circumference butalso to fill the channels longitudinally over a great deal or all oftheir length.

The occlusions of the present invention cause no negative reactionbecause there are no monomeric or toxic material that could causeirritation nor any exotherm that could thermally denature thesurrounding tissue. Thus the closure can be effected with a minimum oftrauma to the host.

With respect to male contraception, it should be noted that the vasdeferens are maintained at a temperature slightly below bodytemperature. This should create no problems with respect to the use ofthe same polymers in that the polymers will solidify at bodytemperature. Since the vas deferens are maintained at a temperatureslightly below 37° C., the polymers should solidify slightly morequickly. However, the polymer will be somewhat more difficult to removein that it is maintained at a lower temperature, i.e., a temperatureslightly below 37° C. Therefore, slightly more heat and/or more fattyacid ester oils may be needed in order to make the polymer flowable andremove the polymer plug from the vas deferens.

Method of Closing off a Supply of Blood

Any of the conditions described earlier, i.e. hemorrhage control,correction of vascular abnormalities, etc. can be treated with thematerials disclosed in this invention as described in connection withFIG. 4. The first step is to "snake" a guided catheter 10 into andthrough the vessels of the circulatory system such that the end of thetip, fitted with a small resistive element 12 and source wires 13, is innear proximity to the defect to be repaired. Next, a solid form of thechannel occluder 14 is fed through the catheter until it comes incontact with the heater portion of the catheter. Enough current ispassed through the resistive heater to transform the solid channeloccluder to its liquid phase 15 as it passes out of the end of thecatheter. Thereupon, the liquid flows into the lumen of the vessel orabnormality in need of repair. Heat is transferred from the liquid tothe surrounding blood supply and tissue and is transformed back to itssolid form that forms a complete seal or occlusion within the vesselwall. The stock solid rod can be fed slowly through the heater until therepair is complete. The catheter can then be removed with assurance thatthe plug will not attach itself to the catheter end and that the repairhas been made. Alternately, a stream of liquid channel occluder can befed through the catheter.

Method of Affixing a Prosthetic Device within a Bone Channel

A new femoral ball end can be secured in the end of prepared femor usingthe materials disclosed in this invention. By referring to FIG. 5, andsubsequent figures, the procedure can be described. The defectivesuperior joint 16 is removed and a portion of the channel 17 within thelongitudinal section of the femor 18 is enlarged at the expense of thebone cells of the femor and the soft tissue 19 normally residing withinthe femor. Once the channel has been enlarged sufficiently to accept theplacement of the prosthetic device, a quantity of polymeric channeloccluder 20, shown in FIG. 6, is heated to about 50° C. and injectedinto the lower end of the enlarged channel. The preheated prostheticdevice 21 is plunged into the liquefied occluder mass forcing the massto flow around the prosthetic device and along the channel walls. InFIG. 7 the prosthetic device is positioned at its proper angle and heldin that position for a few minutes. The heat sink capacity of the bodycontinually draws heat from the liquefied channel occluder mass 20 untilthe temperature of that mass cools below the melting transitiontemperature. At that time the occluder hardens and the prosthetic deviceis fixed in place.

Polymeric Materials

A wide range of different polymeric materials can be used in connectionwith the present invention. However, the materials must be biocompatibleand non-immunogenic in order to avoid irritation and adverse reactionswhen the materials are inserted within the channels to be blocked. Inaddition to these general characteristics, the polymers must have veryspecific characteristics with respect to their first order transitionpoint. More specifically, the polymers must be designed such that theyare solid and non-flowable at body temperature and below. Preferably,the materials are non-flowable at temperatures 2 to 3 centigrade degreesabove body temperature so that they do not become flowable when theindividual having the materials therein increases its temperature abovenormal, i.e., runs a fever or exercises vigorously. The exacttemperature at which the polymers should become flowable will varydepending upon the mammal. In humans, the polymers are designed so thatthey are flowable above 39° C. or at most flowable at a temperature ofabout 45° C. If the polymer does not become flowable at a temperature of45° C. and must be heated above that temperature, then the polymercannot be safely be brought into contact with the mucus membrane surfaceof the channel to be blocked. Temperatures above 45° C. will frequentlydamage the tissue and defeat much of the purpose of the invention.

The polymers are also designed such that they can be melted so that theyare flowable slightly above body temperature but solidify when cooled tobody temperature. Polymeric materials used such as those used inconnection with this invention are good diffusers of heat. Accordingly,when brought into contact with the body tissues, they cool quickly andtherefore quickly solidify. This is important in order to reduce patienttrauma and discomfort.

GENERAL CHARACTERISTICS AND FEATURES OF THE POLYMERS AND THEIRCOMPOSITES

Polymers used in this invention preferably have the followingattributes:

Sharp melting point behavior. The polymeric materials will be in theliquid state within a 10° C. increase over the initial signs of melting.

The position of the melting phenomenon will fall between 30° C. and 50°C., preferably between 34° C. and 45° C. and even more preferablybetween 38° C. and 42° C.

Viscosities @ 50° C. (without filler) will be no greater than 1,000,000centipoise.

The sharpness of the melting point will vary. In general, it will beslightly broader as the molecular weight increases. This is more readilynoticed with main chain crystalline polymers than with side chaincrystalline polymers.

The most common and most optimum position of the melting point has beenfound to be at 40°±2° C. This value can be best identified by using theDifferential Scanning Calorimeter. The position of the peak endotherm,when raised at 10° C. per minute, is correlated with the melting point.

Viscosity is a subjective feature. On one hand, the less viscous thematerial is, the better chance it has (1) to pass through a narrow boreof the applicator and into the channel and (2) to wet and fill the microcontours of the channels that it is filling. On the other, the moreviscous the material is in the liquid state, (1) the less likely thematerial will run out of the vessel before it sets up and (2) the betterit will suspend any filler or radio opaque substance that material maycontain. The decision must be made on a case-by-case basis. A generallypreferred place to start is with polymers that have molecular weightshigh enough to impart a viscosity of about 50,000 to 100,000 centipoiseat 50° C. Filling very fine vessels using very fine cannula wouldsuggest that a lower viscosity be used. Filling major bones such as afemur may well warrant the use of a much higher viscosity material.

The rate at which these polymers crystallize is extremely important tothe practical application of the present invention. If the preplugcrystallizes to quickly, it may even solidify in, say, the needle of theapplicator. If it passes through he applicator it still may crystallizetoo fast in, say, the channel. A test of what is too rapid an onset ofcrystallization can be shown in this example: a channel such as thecanaliculus of a dog is being occluded. A material that is beinginjected has a set time of 5 seconds. It takes 4 seconds for thepolymeric material to flow through the needle stock. The first materialto reach the canaliculus begins to harden after the first second.Additional material continues to be pumped into the canal at the samerate but now that the canaliculus is already partially blocked, the wallbegins to extend beyond its normal dimension. A distended wall is a signthat the set time for this particular application is not long enough andthat an adjustment in syntheses will be needed to provide material oflonger set times.

If the set time is too long or if the melting point is too low, thematerial will never set up or will be washed away by the mechanicalforces within the body or the universe before it has a chance topermanently occlude the channel in which it was placed. For anapplication such as occluding a canaliculus, an ideal crystallizationset time is between one minute and ten minutes, preferably between twominutes and five minutes. By using such materials, the physician isgiven enough time to remove the device from a warming unit, insert thetip of the applicator into the punctum and inject the polymercomposition into the canaliculus. The viscous nature will permit thepolymer composition to remain in the liquid state where it was placedfor five or ten minutes. Therefore, the polymer composition need notcrystallize before then.

SPECIFIC CHARACTERISTICS AND FEATURES OF THE POLYMERS

Main chain crystalline polymers (MCCP's)

These materials have been studied for more than fifty years. Most of thebetter known commercial examples, such as polyethylene, are used belowtheir crystalline melting point where they are tough and strong. Mostsuccessful commercial members have high first order transitions (usuallywithin the range of 75° C. to 320° C.) in order to enjoy a broad use orservice temperatures. Only those main chain crystalline polymers whichhave melting transitions between about 30° C. and about 50° C. can beconsidered for use in this application. Practically, the range is muchnarrower and is dictated by the normal body temperatures and thetemperatures at which tissue injury occurs.

Specific examples of polymers falling in this narrowed meltingtransition range of about 34° C. to 45° C. are:

Poly-2,2,3,3,4,4-hexafluoro-(diamine)-pentamethylene adipate (34° C.)

Poly-tetramethylene succinate (34° C.)

Poly-N,N'diethyl-4,4'-methylenediphenylene sebacamide (34° C.)

Poly-trimethylene malonate (34° C.)

Poly-difluoro-methylene sulfide (35° C.)

Poly-N,N'-diisopropyl 2,2,3,3,4,4-hexafluoro-(diamine)-pentamethyleneadipamide (35° C.)

Poly-oxacyclobutane (trimethylene oxide) (36° C.)

1,4-Poly-cis-2methyl-1,3-butadiene (36° C.)

Poly-4,methyl-(R+)-7, hydroxyenanthic acid (36° C.)

Poly-tetrahydrofuran (tetramethylene oxide) (37° C.)

Poly-trimethylene pimelate (37° C.)

Poly-tetramethylene azelaate (37° C.)

Poly-hexamethylenedithiotetramethylene disulfide (38° C.)

Poly-hexamethyleneoxymethylene oxide (38° C.)

Poly-trimethylene glutarate (39° C.)

Poly-tetramethylene disulfide (39° C.)

Poly-methyleneoxypentamethylene oxide (39° C.)

Poly-diethyl-dimethyl-(Si)-O-phenylene disiloxanylenedipropionamide (40°C.)

Poly-O-phenylene disiloxanylenedipropionamide (40° C.)

Poly-N,N'diethyl-4,4'-methyenediphenylene azelaamide (41° C.)

Poly-trimethylene suberate (41° C.)

Poly-cis-1,4-cyclohexylenedimethylene azelaate (41° C.)

Poly-pentamethylene azelaate (41° C.)

Poly-trans-1,4-cyclohexylenedimethylene Pimelate (42° C.)

Poly-tetrafluoro-ethylene oxide (42° C.)

Poly-isobutene (44° C.)

Poly-isotactic cis-1,3-pentadiene (44° C.)

Poly-pentamethylene disulfide (44° C.)

Poly-oxydiethylene sebacate (44° C.)

Poly-cyclopropylidenedimethylene oxide (45° C.)

Poly-ethylene p-(carboxyphenoxy)-caproate(45° C.)

Poly-N,N'-dibutyl-3,3'-dimethyl-(diamine)-4,4'-methyenediphenyleneadipamide (45° C.)

Poly-N,N'-diisoamyl-3,3'-dimethyl-(diamine)-4,4'-methyenediphenyleneadipamide (45° C.)

Poly-decamethylene disulfide (45° C.)

Poly-trimethylene adipate (45° C.)

Poly-2,2-dimethyl-(diol)-trimethylene adipate (45° C.)

Preferred main-chain crystallizable polymers include water-insolublepolyalkylene oxides, lower alkyl polyesters and polytetrahydrofuran.

Oligomeric MCCP's

The above are examples of homopolymers that have suitable first ordertransitions for the instant invention. Not mentioned are a myriad ofcopolymers that could be synthesized from various ratios of monomersthat would exhibit first order transitions in this very temperaturerange. Of course, they too would be very applicable.

Smaller fragments of polymers known as oligomers can also be used in thepresent invention. For example short chain lengths of polymethylene,H--(CH₂)_(n) --H, exhibit melting transitions according to specificchain lengths.

When n=19 then Tm=32° C.-34° C.

n=20 then Tm=36° C.-38° C.

n=21 then Tm=40° C.-42° C.

n=22 then Tm=43° C.-45° C.

n=>10⁴ then Tm=143° C.-145° C.

Hence, for many high molecular weight polymers whose melting point isabove the desired and specified range, one need only produce theappropriate oligomer to obtain a transition of the correct temperaturevalue.

Side-chain crystallizable polymers (SCCP's)

Side-chain crystallizable polymers, sometimes called "comb-like"polymers, are well-known and available commercially. These polymers arereviewed in J. Polymer Sci.: Macromol. Rev. 8:117-253 (1974), thedisclosure of which is hereby incorporated by reference. In general,these polymers contain monomer units X of the formula: ##STR1## whereinM is a backbone atom, S is a spacer unit and C is a crystallizablegroup. These polymers generally have a heat of fusion (WH_(f)) of atleast about 10 Joules/g. The polymers can be copolymers and will contain20 to 100 wt. % of the monomer units drawn above and are represented by"X". If the polymer contains less than 100% X, it will in additioncontain monomer units which may be represented by "Y" or "Z", or both,wherein Y is any polar or nonpolar monomer or mixture of polar ornonpolar monomers capable of polymerizing with X and/or Z, and wherein Zis a polar monomer or mixture of polar monomers. These polarmonomers--e.g., polyoxyalkylenes, acrylates includinghydroxyethylacrylate, acrylamides and methacrylamides--will typicallyincrease adhesion to most substrates. If the polar species "Z" isacrylic acid, it is preferred that it comprise about <10 wt. % of thepolymer.

The backbone of the polymer (defined by "M") may be any organicstructure (aliphatic or aromatic hydrocarbon, ester, ether, amide, etc.)or an inorganic structure (sulfide, phosphazine, silicone, etc.), andmay include spacer linkages which can be any suitable organic orinorganic unit, for example ester, amide, hydrocarbon, phenyl, ether, orionic salt (e.g., a carboxyl-alkyl ammonium or sulphonium or phosphoniumion pair or other known ionic salt pair).

The side-chain (defined by "S" and "C") may be aliphatic or aromatic ora combination of aliphatic and aromatic, but must be capable of enteringinto a crystalline state. Common examples are: linear aliphaticside-chains of at least 10 carbon atoms, e.g., C₁₄ -C₂₂ acrylates ormethacrylates, acrylamides or methacrylamides, vinyl ethers or esters,siloxanes or alpha olefins; fluorinated aliphatic side chains of atleast 6 carbons; and p-alkyl styrene side chains wherein the alkyl is of8 to 24 carbon atoms.

The length of the side-chain moiety is usually greater than 5 times thedistance between side-chains in the case of acrylates, methacrylates,vinyl esters, acrylamides, methacrylamides, vinyl ethers and alphaolefins. In the extreme case of a fluoroacrylate alternate copolymerwith butadiene, the side-chain can be as little as two times the lengthas the distance between the branches. In any case, the side-chain unitsshould make up greater than 50% of the volume of the polymer, preferablygreater than 65% of the volume.

Specific examples of side-chain crystallizable monomers are theacrylate, fluoroacrylate, methacrylate and vinyl ester polymersdescribed in J. Poly. Sci, 10.3347 (1972); J. Poly. Sci. 10:1657 (1972);J. Poly. Sci. 9:3367 (1971); J. Poly. Sci. 9:3349 (1971); J. Poly. Sci.9:1835 (1971); J.A.C.S. 76:6280 (1954); J. Poly. Sci. 7:3053 (1969);Polymer J. 17:991 (1985), corresponding acrylamides, substitutedacrylamide and maleimide polymers (J. Poly. Sci.: Poly. Physics Ed.11:2197 (1980); polyolefin polymers such as those described in J. Poly.Sci.: Macromol. Rev. 8:117-253 (1974) and Macromolecules 13:12 (1980),polyalkyl vinylethers, polyalkylethylene oxides such as those describedin Macromolecules 13:15 (1980), alkylphos phazene polymers, polyaminoacids such as those described in Poly. Sci. USSR 21:241, Macromolecules18:2141, polyisocyanates such as those described in Macromolecules 12:94(1979), polyurethanes made by reacting amine- or alcohol-containingmonomers with long-chain alkyl isocyanates, polyesters and polyethers,polysiloxanes and polysilanes such as those described in Macromolecules19:611 (1986), and p-alkylstyrene polymers such as those described inJ.A.C.S. 75:3326 (1953) and J. Poly. Sci. 60:19 (1962).

Of specific utility are polymers which are both relatively polar andcapable of crystallization, but wherein the crystallizing portion is notaffected by moisture. For example, incorporation of polyoxyethylene,polyoxypropylene, polyoxybutylene or copolyoxyalkylene units in thepolymer will make the polymer more polar, improving adhesion to moistskin.

Hydrophilic monomers are beneficially added to the polymer if it isdesired to increase the MVTR properties of the occluding material.Commonly used hydrophilic comonomers include acrylic acid, acrylamide,hydroxy alkyl (meth)acrylates such as hydroxy ethyl acrylate, hydroxyethyl methacrylate and hydroxy butyl acrylate, alkoxy (meth)acrylatessuch as ethoxy ethyl acrylate, ethoxy ethoxy ethylacrylate,ethyltriglycol methacrylate, 3-methoxy butylacrylate and the like. Apreferred class of high MVTR inducing monomers are derivatives ofpolyethylene glycol of with molecular weights ranging from 50 to 5,000.Commonly these units may be incorporated either into the backbone or aspendant groups.

Moisture vapor transmission rates and/or absorptive properties of theoccluding material may be modified by the incorporation of soluble orinsoluble hydrophilic materials, for example by addition ofcarboxymethyl cellulose, guar gum, carragenan, cellulose based orsynthetic fibers and the like.

In a particularly preferred embodiment herein, in the above structure,--C is selected from the group consisting of --(CH₂)_(n) --CH₃ and--(CF₂)_(n) --CF₂ H, where n is an integer in the range of 6 to 21inclusive, --S-- is selected from the group consisting of --O--, --CH₂--, --(CO)--, --O(CO)-- and --NR-- where R is hydrogen or lower alkyl(1°-16° C.), and --M-- is -- (CH₂)_(m) --CH!-- where m is 0 to 2.

Typical "Y" units include linear or branched alkyl or aryl acrylates ormethacrylates, alpha olefins, linear or branched.alkyl vinyl ether orvinyl esters, maleic esters or itaconic acid esters, acrylamides,styrenes or substituted styrenes, acrylic acid, methacrylic acid andhydrophilic monomers as detailed in WO84/0397, cited supra.

Some specific examples of side chain crystalline homopolymers which aresuitable for inclusion in the present invention are:

Poly-dodecylvinyl ether (33° C.)

Poly-1,1-dihydroperfluoro-octyl-acrylate (35° C.)

Polycapryl-aldehyde (35° C.)

Poly-1-decene (40° C.)

Poly-trans-1,2-dichloro-dodecamethylene (40° C.),

Poly-vinyl palmitate (41° C.)

Poly-hexadecyl-acrylate (43° C.)

Poly-1-dodecene (45° C.)

Poly-N-hexadecyl-acrylamide (45° C.)

In addition to the above-described monomer units "M--S--C", monomerstructures given by ##STR2## may in addition, or in the alternative, bepresent in the polymer as: ##STR3##

"D" is a hydrophilic polyether chain such as a polyoxyalkylene chain(e.g., polyoxyethylene) which, in contrast to "C", may or may not becrystallizable.

It is important in the case of polyolefins, which can exist in aplurality of tactic forms, that in order to effect the sharpness oftransition between solid and liquid states the tacticity of the polymermust be carefully selected. The polymer can be present in a singularconfiguration, i.e., either atactic, syndiotactic or isotactic, but notin a mixture of tacticities unless their melting pointsopportunistically coincide. Having a mixture of various tacticpolymerswith different melting points will broaden the transition and cause theresultant polymer to exhibit sluggish melting property changes over anarrow temperature range.

Random and block SCCP's

When two or more monomer units are used to synthesize the SCCP, it canbe represented as: ##STR4## Here the two monomer units can be arrangedrandomly or in blocks. One or both of the units "a" and "b" may becrystalline.

Graft SCCP's

Still another way of utilizing or arranging these SCCP's is to graftthem as hard blocks onto another backbone. (--P--) ##STR5##

The backbone chain (--P--) can either be derived from an additionmechanism or from a condensation process. It could also be a side chaincrystalline polymer but usually it will be a backbone without anyability to crystallize above room temperature. In that state it will bereferred to as the "soft" block. In the present invention, we have usedbutyl acrylate as an example of the backbone chain. The grafted SCCblocks can be constructed of all the same monomer units or they could berandom or block copolymers. In this present invention we have madeexamples in which the SCC block was either pure poly octadecyl (C₁₈)methacrylate or copolymers of octadecyl and docosyl (C₂₂) methacrylate.Furthermore, bimodal melting can be achieved by constructing grafts withsome SCC moieties of pure octadecyl ester and with some SCC moieties ofpure docosyl ester. The graft configuration of atoms offers a number ofspecific advantages which will be discussed below.

Control of first order transition temperature

Assuming that the graft consists of a SCCP block and a non crystallinebackbone, the melting point will be determined entirely by the choiceand ratio of monomers used to make up the hard block. Hence, sharp firstorder transitions can be achieved from about 34° C. when only octadecylmethacrylate derived blocks are used to about 45° C. when equal parts byweight of octadecyl and docosylmethacrylate are employed.

Control of recrystallization time

Most polymers that have melting points in the 30° C. to 50° C.temperature range will undergo crystallization within a few secondsafter they have been lowered a few degrees below their normal meltingtemperature. By varying the ratio between soft non-crystalline backboneblock and hard SCCP block, a kinetic lag can be built into the system.As an example, we are able to show that recrystallization times of 0-16seconds @ 25° C. are exhibited when hard blocks of polyoctadecylcohexyldecylacrylate are used and constitute 40 to 100% of thegraft (Poly butyl acrylate is the soft block). When a hard block ischanged from octadecyl acrylate to octadecyl methacrylate, thecrystallization time of the block copolymer with 40% hard blocklengthens to 73 seconds. It must be pointed out that allrecrystallziation times were measures at 25° C. and thatrecrystallization time is shortened as the first order transitiontemperature is increased above the measuring temperature. When theconcentration of hard block is further reduced to 30% and then to 20%,lag times of 97 and 154 seconds are achieved.

Experimental:

Melting temperatures were determined using Differential Scanningcalorimetry (DSC) at a heating rate of 10° C./min.

Lag times or onset of crystallization are measured as follows: A sampleof the material under test is melted and drawn down on a flat steelsurface with a "blade" such that a uniformly thick film of 10μ isproduced. The coated steel plate is then placed in an oven for 15minutes and allowed to achieve a temperature of 60° C. The sample isremoved and placed on a cooling plate that is maintained at 25° C. bymeans of thermostated, circulating water supply. A stop watch is begunimmediately on contact. A small glass rod, 2 mm in diameter is dippedinto the film and then pulled out. While the material is in thenon-crystalline phase, small fine strings can be pulled from the film.As soon as the material experiences any significant amount ofcrystallization, it becomes impossible to pull anything from thesurface. It is at this precise time when one observes the sharptransition from a flowable state to a non-flow one that the time isrecorded.

EXAMPLES

The following examples are put forth so as to provide those of ordinaryskill in the art with a complete disclosure and description of how tomake and formulate polymers of the invention and are not intended tolimit the scope of what the inventors regard as their invention. Effortshave been made to ensure accuracy with respect to numbers used (e.g.,amounts, temperatures, molecular weights, etc.), but some experimentalerrors and deviation should be accounted for. Unless indicatedotherwise, part are parts by weight, molecular weight is weight averagemolecular weight, temperature is in degrees centigrade and pressure isat or near atmospheric.

SPECIFIC EXAMPLES OF POLYMER FORMULATIONS Example 1

Main chain crystalline polymer composites

A mixture of 93 parts of Poly-cis-isoprene (M.W. 800,000; Aldrich ChemCo.) and 7 parts of silver powder (Johnson Matthey) was made by addingthe polymer and the filler to 100 parts of toluene, heating thesuspension to about 75° C. and then stripping the solvent from theviscous mixture in a rotating evaporating unit under 21 mm Hg pressure.A constant temperature bath was used to keep the mixture above 70° C.When all the solvent was removed the temperature was lowered to 50° C. Aglass rod was dipped into the viscous syrup. The temperature was allowedto cool slowly over the course of several hours. When the temperaturecooled below 35° C., the rod was no longer able to be turned in relationto the mass of the polymer. The rod had become locked in place. Theflask containing the composite and the rod was reheated to about 45° C.The rod could be easily extracted. The rod which now contained a thickcoating of the composite was allowed to cool to room temperature. Thecoated rod was placed inside an anesthetized dogs mouth. The materialproved to be radio-opaque and was clearly visible against other normalcalcium based structures. This material is near the higher end of thespectrum of viscosities and rate of crystallization for suchapplications as a cast-in-place bone pin anchoring device. Lowermolecular weight materials would flow easier and fill the surfaceinterstices better and quicker.

Examples 2 to 6

The following materials were produced in a similar manner to those inexample 1.

    ______________________________________                                        Example                                                                              Polymer             Filler Ratio F/P                                                                            Melt                                 #      (P)       Source    (F)    (Wt/Wt)                                                                              Pt.                                  ______________________________________                                        2      Poly-     Poly-     Fumed  0.1    43° C.                               tetrahydro                                                                              sciences  silica                                                    furan               (.007μ)                                         3      Poly-     Poly-     none   n/a    37° C.                               tetrahydro                                                                              sciences                                                            furan                                                                  4      Poly-tri- Monomer   none   n/a    40° C.                               methylene Polymer &                                                           glutarate Dajac                                                        5      Poly-tri- Monomer   Gold,  2.5    40° C.                               methylene Polymer & powder,                                                   glutarate Dajac     spherical,                                                                    1.5-3.0μ                                        6      Poly-tri- Monomer   Silver 1.5    45° C.                               methylene Polymer & powder                                                    adapate   Dajac                                                        ______________________________________                                    

These two polymers and three composites had viscosities which permittedthem to be forced through a 16 gauge hypodermic needle when they wereabove the melting point. They all crystallized rapidly upon cooling tojust below their melting point.

Examples 7 to 9

Use of an oligomeric fraction of Poly-methylene as a castable plug

A syringe fitted with a small blunted 24 gauge needle was filled withheneicosane, H--(CH₂)₂₁ --H, after it was heated to 50° C. Viscosity=22centipoise @ 3 RPM's and 50° C.; 21 centipoise @3 RPM's and 45° C. Theair was removed by pointing the needle upward and pushing in the plungeruntil the hydrocarbon began to flow out of the tip. Immediately, the tipof the needle was inserted in the right punctum of the superiorcanaliculus of a beagle dog, tranquilized with a solution ofacepromazine, and about 10 mg of the oligomer was introduced. Thematerial instantly set up into a solid mass beneath the thinsemi-transparent tissue surrounding the punctum. The experiment wasrepeated only this time the heneicosane contained three times its weightof Gold, (powder, spherical, 1.5-3.0μ). Some difficulty was experiencedbecause the gold would tend to settle out while the olefin was in theliquid state. Nevertheless, some of the suspension was introduced intothe left punctum of the superior canaliculus of the same beagle dog andwas corroborated by X-ray radiography. The settling of this type ofsuspension was reduced significantly when fumed silica was added to themixture. Unfortunately, the more silica that was added the moredifficult it became to force the mixture through the very fine needle.This oligomeric material represents the lower end of the spectrum ofviscosities for such applications as a cast-in-place device.

    ______________________________________                                                Polymer            Filler Ratio F/P                                                                            Melt                                 Example #                                                                             (P)       Source   (F)    (Wt/Wt)                                                                              Pt.                                  ______________________________________                                        7       heniecosane                                                                             Aldrich  none   n/a    43° C.                                          Chem Co.                                                    8       heniecosane                                                                             Aldrich  Gold,  3.0    37° C.                                          Chem Co. powder,                                                                       spherical,                                                                    1.5-3.0μ                                        9       heniecosane                                                                             Aldrich  Gold + 3.1    40° C.                                          Chem Co. Fumed                                                                         silica                                                                        (.007μ)                                         ______________________________________                                    

Example 10

Preparation of side chain crystalline polymer

A mixture was prepared from 84 parts octadecyl acrylate containing atleast 90% octadecyl chains (with all the remaining chains greater than14 carbon atoms in length), 16 parts butyl acrylate and 1.86 partsdodecyl mercaptan. To a reactor maintained at 100° C. was added thismixture at a rate of 14.5 ml/min simultaneously with t-butyl peroctoatethat was added at a rate of 0.15 ml/min. The reaction mixture wasallowed to react for an additional 2 hours after the addition wascomplete. The product was removed from the reactor and underwentmultiple (2×) reprecipitations from a solvent/nonsolvent mixture(toluene/ethanol). The final purified product was dried under reducedpressure yielding 80 parts of sample 10. GPC analysis againstpolystyrene standards yields an Mw=18,900, Mn=11,800 and Mw/Mn=1.6.Extraction analysis yielded the following residuals: 374 ppm ofoctadecyl acrylate and <130 ppm of butyl acrylate. DSC analysis shows afirst heat endothermic peak at 40.5° C. and second heat endothermic peakat 38.6° C. Viscosity analysis on a Brookfield LVT viscometer usingspindle 18/13R yielded the following viscosities: 1530 centipoise @ 0.3RPM's and 50° C.; 2300 centipoise @ 0.3 RPM's and 45° C.

Examples 11 to 17

The following materials were produced in a similar manner to that inexample 10. The appropriate choice of reactant ratios and different sidechain lengths allows variation of the SCC polymer melt temperaturethroughout the bioeffective range of about 30°-50° C.

    ______________________________________                                                Formulation                                                                   (parts by wt.)           Second Heat Tm                               Sample #                                                                              C18A/C4A/C12SH                                                                             Mw (Daltons)                                                                              (°C.)                                 ______________________________________                                        11      96/4/1.86    16,800      44.5                                         12      92/8/1.86    19,600      44.5                                         13      89/11/1.86   20,500      40.2                                         14      88/12/1.86   21,800      40.6                                         15      86/14/1.86   31,300      38.4                                         16      80/20/1.86   17,900      36.3                                         17      76/24/1.86   17,900      35.0                                         ______________________________________                                    

Example 18

Preparation of the polyoctadecyl-cohexadecyl acrylate hard block.(macromer) A solution was prepared from 92 g octadecyl acrylate (minimum95% octadecyl chains), 8 g of hexadecyl acrylate (minimum 95% hexadecylchains) 3.8 g mercaptoethanol, 200 ml toluene and 1.0 gazobisisobutyronitrile (AIBN). The stirred solution was heated to 60° C.under a nitrogen blanket for 14 hours. The solution was then heated todestroy residual AIBN followed by addition of 8.5 gisocyanatoethylmethacrylate. One drop of dibutyl tin dilaurate wasadded. Stirring at room temperature was continued for 16 hours. Thepolyoctadecyl methacrylate macromer was precipitated from the solutionwith ethanol. It was filtered and dried under reduced pressure. GPCanalysis indicated the following: Mw=3888, Mn=2936 and Mw/Mn=1.32. DSCanalysis shows a second heat endothermic peak at 41.6° C.

Examples 19 to 25

Preparation of other hard block macromers

They have been prepared to vary the Tm within the bioeffective range. Tmvariation within the bioeffective range is readily accomplished throughappropriate choice of polymer side chain length. The following materialswere produced in a similar manner to that in example 18.

    ______________________________________                                        Formulation (% by wt)          2nd Heat                                       Sample #                                                                              C16A   C18A    C18M  C22M   Mw   Tm(°C.)                       ______________________________________                                        19             100                  3900 44.8                                 20              0      100          3900 35.6                                 21             15      85           3600 35.7                                 22             25      75           3900 36.8                                 23                     66    34     4300 41.8                                 24                     60    40     3400  37.43                               25      8      92      55    45     3900  41.62                               ______________________________________                                    

Example 26

Preparation of SCC polymer Thermoplastic Elastomer (TPE)

A graft copolymer (polybutyl acrylate-g-polyoctadecyl acrylate) wasprepared using the polyoctadecyl acrylate macromer of example 18. Asolution was prepared from 20 g of the above macromer, 30 g of butylacrylate, 100 ml of toluene, 0.2 g of dodecyl mercaptan and 0.5 g ofAIBN. The solution was heated to 60° C. under nitrogen blanket for 14hours. The TPE graft copolymer was precipitated from solution with coldethanol, filtered and dried under reduced pressure to yield 40 g of theproduct sample. GPC analysis indicates the following: Mw=40,400Mn=18,000 and Mw/Mn=2.24. Residue analysis indicates; butyl acrylate 624ppm; octadecyl methacrylate 562 ppm. DSC analysis shows a second heatendothermic peak at 41.3° C. Time @ 25° C. to onset ofcrystallization=16 seconds. Viscosity (LVT w/spindle #4)=7200 centipoise@ 3 RPM's and 50° C.; 16000 centipoise @ 3 RPM's and 46° C.

Examples 27 to 40

Preparation of other Graft SCC polymers (Thermoplastic Elastomers)

These polymers have been prepared to vary the Tm within the bioeffectiverange as well as the onset of crystallization time. Tm variation withinthe bioeffective range is readily accomplished through appropriatechoice of polymer side chain length and the relative ratio between thehard and soft block. The following materials were produced in a similarmanner to that in example 26.

    ______________________________________                                                       Macromer        Second Time @ 25° C.                    Sample         to C4A          Heat   to onset of                             #     Macromer ratio    Mw     Tm(°C.)                                                                       crystallization                         ______________________________________                                        27    19       40/60    184,000                                                                              43.0   >15                                     28    19       40/60    48,000 41.7   >15                                     29    19       40/60    103,00 42.7   >15                                     30    20       40/60    40,000 41.3   16                                      31    20       40/60    80,000 41.3   24                                      32    21       40/60    48,000 32.8   54                                      33    22       40/60    52,000 32.8   29                                      34    22       30/70    56,000 31.7   51                                      35    18       30/70    55,000 28.9   97                                      36    22       20/80    57,000 31.4   135                                     37    18       20/80    53,000 28.8   154                                     38    23       40/60    54,900 42.8   25                                      39    23       30/70    63,800 41.9   25                                      40    23       20/80    63,100 40.3   17                                      41    23       30/70    95,500 43.0   20                                      ______________________________________                                    

Example 42

Material made in example 41 was blended with gold (powder, spherical,1.5-3.0μ) power as described in example 5. The composite was heated to50° C. and loaded into a small hydraulic applicator with an exit portconsisting of a drilled hole using a number 80 drill. The applicator andits charge were allowed to cool. At room temperature no material couldbe released from the applicator even when high pressure was exerted. Theapplicator and its charge was then heated in a cup of warm water (˜50°C.). The tip of the applicator was inserted in the left punctum of thesuperior canaliculus of a beagle dog that had been tranquilized with asolution of acepromazine and about 10 mg of the composite was introducedthrough the narrow portal. The material flowed into the canaliculusbeneath the thin semi-transparent tissue surrounding the punctum. Withina few minutes the dog was x-rayed and the plug was clearly seen. After60 day, the plug remained in exactly the same position. At this time 10cc of warm (46° C.) isotonic sterile saline solution was used to flushout the cast-in-place-plug.

Example 43

Experiment 42 was repeated only using the polymeric material produced inexample 33. When an x-ray was taken after 3 hours, a plug was clearlyvisible. When an x-ray was taken after 48 hours, there was no evidenceof any plug remaining. It can be deduced that, for this area of themammalian body, the particular sample possessed a melting point that wasbelow the normal tissue temperature. Therefore, it never resolidifiedand was unstable. On the other hand, the experiment described in example42 demonstrates that stabilization of the position within thecanaliculus by recrystallization of sample 41 did occur.

The instant invention is shown and described herein in what isconsidered to be the most practical, and preferred embodiments. It isrecognized, however, that departures may be made therefrom which arewithin the scope of the invention and that obvious modifications willoccur to one skilled in the art upon reading this disclosure.

I claim:
 1. A channel occluding unit for occluding a channel having amaximum temperature T_(L) in a living mammal, the unit comprisinganinjecting device; and a thermoplastic, biocompatible, non-immunogenicoccluding composition in the injecting device, the composition,(a)having a melting point which is(i) below 50° C. and (ii) such that thecomposition is flowable at a temperature which does not damage thechannel, (b) having a freezing point which is(i) above 30° C. and (ii)such that the composition is non flowable at T_(L), (c) comprising athermoplastic polymer, and (d) being injectable, while it is flowable,from the device into the channel, to form a plug which occludes thechannel and which can be removed from the channel by heating to atemperature at which the composition is flowable.
 2. A channel occludingunit of claim 1 wherein the polymer is a polymer which, when cooled fromabove the melting point to below the freezing point, becomes acrystalline solid.
 3. The channel occluding unit of claim 1, furthercomprising:a means for heating the occluding composition within theinjecting device to a temperature such that the occluding compositionbecomes flowable.
 4. The channel occluding unit of claim 1, wherein theoccluding composition is a non-flowable solid at a temperature of about45° C. or less and is flowable at a temperature of about 46° C. or more.5. The channel occluding unit of claim 1, wherein the occludingcomposition is flowable at a temperature of 10° C. or less above thebody temperature of the mammal and is non-flowable at the bodytemperature of the mammal.
 6. The channel occluding unit of claim 1,wherein the polymer is selected from the group consisting of a mainchaincrystalline polymer; and a graft copolymer.
 7. The channel occludingunit of claim 1, wherein the polymer is a sidechain crystalline polymerhaving a melting point between 34° and 45° C.
 8. The channel occludingunit of claim 1 wherein the polymer is a thermoplastic elastomercomprising(i) a backbone which does not crystallize above roomtemperature, and (ii) sidechain crystalline polymeric blocks whichextend from the backbone.
 9. A device for occluding a channel in a humanbeing, the channel having a maximum temperature T_(L), the devicecomprisinga chamber having at least one orifice therein; athermoplastic, biocompatible, non-immunogenic occluding composition inthe chamber, the occluding composition having a melting point whichis(i) sufficiently high that the occluding composition is non-flowableat temperatures experienced by human beings, and (ii) sufficiently lowthat it can be melted and brought into contact with the cells of a humanbeing without damaging the cells, the occluding composition being (a)non-flowable at T_(L), and (b) flowable when heated to a temperaturewhich does not damage the channel, and the occluding compositioncomprising a thermoplastic polymer; and a means for propelling theoccluding composition out of the chamber, through the orifice, and intothe channel, to form a plug which occludes the channel and which can beremoved from the channel by heating to a temperature at which thecomposition is flowable.
 10. The device of claim 9, further comprising:ameans for raising the temperature of the occluding composition to atemperature where the occluding composition becomes flowable.
 11. Thedevice of claim 9 wherein the polymer is a sidechain crystalline polymerhaving a melting point between 34° and 45° C.
 12. The device of claim 9wherein the polymer is a thermoplastic elastomer comprising(i) abackbone which does not crystallize above room temperature, and (ii)sidechain crystalline polymeric blocks which extend from the backbone.13. A device for occluding a channel in a living mammal, the channelhaving a maximum temperature T_(L), the device comprising:(a) aninjector comprising a chamber; (b) a thermoplastic, biocompatible,non-immunogenic occluding composition within the chamber, the occludingcomposition having a melting point which is(i) sufficiently high thatthe occluding composition is non-flowable at T_(L), and (ii)sufficiently low that melted occluding composition can be injected intothe channel without damaging the mammal; and (c) means for removingmelted occluding composition from the chamber and injecting it into thechannel in a sufficient quantity to form a plug which at least partiallyoccludes the channel and which can be removed from the channel byheating to a temperature at which the composition is flowable.
 14. Thedevice of claim 13 including means for heating the occluding compositionin the chamber to a temperature higher than the melting point of theoccluding composition.
 15. The device of claim 13 wherein the polymer isa sidechain crystalline polymer having a melting point between 34° and45° C.
 16. The device of claim 13 wherein the polymer is a thermoplasticelastomer comprising(i) a backbone which does not crystallize above roomtemperature, and (ii) sidechain crystalline polymeric blocks whichextend from the backbone.
 17. A device for occluding a canaliculuslacrimalis in a human being, the device comprising(a) a chamber, (b)within the chamber, a thermoplastic, biocompatible, non-immunogenicoccluding composition comprising a sidechain crystalline polymer havinga melting point between 38° and 43° C.; (c) a heater for melting theoccluding composition within the chamber; and (d) means for removingmelted occluding composition from the chamber and injecting it into thecanaliculus lacrimalis.
 18. A device according to claim 17 wherein thepolymer is a thermoplastic elastomer comprising(i) a backbone which doesnot crystallize above room temperature, and (ii) sidechain crystallinepolymeric blocks which extend from the backbone.
 19. A device accordingto claim 18 wherein the occluding composition contains particles of goldas a filler.